Project Summary Medical imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have been widely used in studying the underlying mechanisms of mental illnesses and neurological disorders such as brain tumors, Alzheimer?s disease, epilepsy, and depression, etc. However, PET and MRI scans are almost always ordered as separate studies on separate machines, often resulting in weeks of delay in acquiring critical information about a patient?s disease. The recent rise of hybrid PET/MRI has enabled the simultaneous acquisition of anatomical, functional, and molecular information about the patient. However, its accessibility is limited by the high cost ($5M) of the commercial permanently integrated PET+MRI systems (+ an additional $1.5-2M room renovation cost). Today, only about 40 PET/MRI systems are installed in the US compared to almost 13,000 installed MRI systems. Moreover, the design and geometry of the commercial whole- body PET/CT and PET/MRI systems are not optimized for brain imaging, resulting in poorer sensitivity and spatial resolution achievable for neurological studies. To address these needs, PETcoil is proposing to develop a portable PET insert that can be installed into (and removed from) any existing MRI systems to achieve simultaneous PET/MRI for a fraction of the cost compared to installing an integrated PET+MR system. In addition to significantly lower cost, the proposed PET insert also provides 3 times higher photon sensitivity and 4 times finer volumetric spatial resolution compared to state-of-the-art whole-body integrated PET+MR systems. Key to facilitating this removable insert concept is the novel ?radiofrequency (RF)-penetrable? technology we have developed at Stanford. In this Phase I project, we will create a compact and scalable design of the PET detector module ready for scaling up to a full RF-penetrable PET insert system for a Phase II proposal. We will also validate the MRI compatibility of the PET detector modules by comparing the PET and MRI performance results acquired with the PET detector modules outside the MRI system to those acquired inside 3 MRI systems under simultaneous PET and MRI operation. The success of this project will mitigate risks toward the commercialization of the first portable time-of-flight (TOF) RF-penetrable PET scanner insert that leverages existing MRI systems to achieve simultaneous TOF-PET/MR brain imaging, without requiring modifications to the MR system hardware. The proposed portable PET insert can greatly disseminate PET/MRI for brain imaging and facilitate the research and clinical characterization of a wide variety of neurological disorders.